Compositions and methods for prophylactic and therapeutic supplementation of nutrition in subjects

ABSTRACT

The present invention relates to compositions without added iron and methods for prophylactic nutritional supplementation and therapeutic nutritional supplementation. Specifically, the method involves administering to an individual a composition comprising carotenoids, vitamin E, vitamin D, vitamin C, thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin, pantothenic acid, cobalamin, magnesium, manganese, zinc, selenium, chromium, copper, alpha lipoic acid, and lutein, wherein the composition is free of added iron.

CROSS REFERENCE TO RELATED APPLICATION

[0001] The present invention is related to and, in accordance with theprovisions of 35 U.S.C. §119(e), claims the benefit of provisionalpatent application Serial No. 60/301,443 filed Jun. 29, 2001, which isexpressly incorporated fully herein by reference.

FIELD OF THE INVENTION

[0002] The present invention relates to compositions comprising variousvitamins and minerals, and without added iron, and methods for usingthese compositions for prophylactic nutritional supplementation andtherapeutic nutritional supplementation in, for example, physiologicallystressful conditions and to minimize the effect of exogenous ironsupplementation.

BACKGROUND OF THE INVENTION

[0003] Nutrition plays a critical role in maintaining good health.Proper nutrition prevents dietary deficiencies, and also protectsagainst the development of disease. Proper nutrition plays anincreasingly important role as the body faces physiological stress. Forexample, as the body ages it suffers significant physiological stresses.Specifically, as the body metabolism shifts to accumulating larger fatstores and decreasing lean body mass, this increase in body weight maylead to obesity and associated conditions such as diabetes,cardiovascular disease, hypertension, osteoarthritis, and cancer. Otherconditions, such as anorexia, malnutrition, gastrointestinal disorders,chronic alcoholism, chronic infections, acute infections, congestiveheart failure, hyperthyroidism, poorly controlled diabetes, cheilosis,gingivitis, stomatitis and dietary restrictions, often result inphysiological stresses that may be exacerbated by poor nutrition. Inparticular, these disease states may result in increased oxidativestress or elevated homocysteine levels that further compromise health.

[0004] Thus, nutritional supplementation serves a vital role inprotecting against poor nutrition and disease. More specifically,nutritional supplementation may provide the necessary vitamins,minerals, and other nutrients that might otherwise be lacking in thediet, and provide the nutritional defense against disease development.The invention herein provides for compositions and methods, specificallyusing an iron-free multi-vitamin/mineral/antioxidant formulation,designed to optimize health and wellness, minimize oxidative stress, andnormalize homocysteine levels.

SUMMARY OF THE INVENTION

[0005] The present invention provides nutritional compositions withoutiron and methods of using these compositions for both prophylactic andtherapeutic nutritional supplementation, specifically in physiologicallystressful conditions. Specifically, the present invention relates tonovel compositions of vitamins and minerals, without exogenous iron,that can be used to supplement the nutritional deficiencies observed inpatients with anorexia, malnutrition, gastrointestinal disorders,chronic alcoholism, chronic infections, acute infections, congestiveheart failure, hyperthyroidism, poorly controlled diabetes, cheilosis,gingivitis, stomatitis, and/or dietary restrictions. In addition, thecompositions may be used to treat the nutritional deficiencies ofpatients suffering from a disease state that results in increasedoxidative stress or elevated homocysteine levels.

[0006] The compositions of the present invention include variousvitamins and minerals that improve the nutritional state of a patient;these compositions preferably may be used therapeutically orprophylacticly. The vitamins of the present invention may preferablycomprise one or more of carotenoids, vitamin E, vitamin D₃, vitamin C,thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin,pantothenic acid, and cyanocobalamin. The minerals of the presentinvention may preferably include one or more of magnesium, manganese,zinc, selenium, chromium, and copper. In addition, the present inventionmay preferably comprise other nutritional elements, such as alpha lipoicacid, and/or lutein. The compositions of the present inventionpreferably do not include exogenous iron as an added component.

[0007] In a preferred embodiment, the compositions of the presentinvention comprise carotenoids in a range of about 2400 IU to about 3600IU, vitamin E in a range of about 80 IU to 120 IU, vitamin D in a rangeof about 320 IU to about 480 IU, vitamin C in a range of about 240 mg to360 mg, thiamine in a range of about 16 mg to 24 mg, riboflavin in arange of about 4 mg to about 6 mg, niacin in a range of about 20 mg toabout 30 mg, folic acid in a range of about 0.8 mg to 1 mg, pyridoxineprovided in a range of about 20 mg to 30 mg, biotin in a range of about80 μg to about 120 μg, pantothenic acid in a range of about 12 mg toabout 18 mg, cobalamin in a range of about 40 μg to about 60 μg,magnesium in a range of about 40 mg to about 60 mg, manganese in a rangeof about 1.2 mg to about 1.8 mg, zinc in a range of about 20 mg to about30 mg, selenium in a range of about 80 μg to 120 μg, chromium in a rangeof about 40 μg to about 60 μg, copper in a range of about 1.2 mg toabout 1.8 mg copper, lipoic acid in a range of about 12 mg to about 18mg, and lutein in a range from about 4 mg to 6 mg, wherein thesecompositions are free of added iron.

[0008] In another embodiment of the compositions of the presentinvention, vitamin E is present as d-alpha tocopheryl succinate, vitaminD is vitamin D₃, niacin is niacinamide, chromium is chromium chloride,selenium is present as sodium selenate, zinc is zinc oxide, carotenoidsconsist of alpha-carotene, beta-carotene, cryptoxanthin, lutein andzeaxanthin, magnesium is magnesium oxide, manganese is present asmanganese sulfate, and copper is cupric sulfate.

[0009] In a further preferred embodiment of the present invention, thecomposition includes about 3000 IU carotenoids, about 100 IU d-alphatocopheryl succinate, about 400 IU vitamin D₃, about 300 mg vitamin C,about 20 mg thiamine, about 5 mg riboflavin, about 25 mg niacinamide,about 1.0 mg folic acid, about 25 mg pyridoxine HCl, about 100 μgbiotin, about 15 mg calcium pantothenate, about 50 μg cyanocobalamin,about 50 mg magnesium oxide, about 1.5 mg manganese sulfate, about 25 mgzinc oxide, about 100 μg selenium, about 50 μg chromium chloride, about1.5 mg cupric sulfate, about 15 mg alpha lipoic acid, and about 5 mglutein, wherein this composition is free of added iron.

[0010] In addition, the compositions of the present invention may beadministered to an individual on a daily basis and the composition maybe administered orally. Furthermore, the compositions of the presentinvention may include a pharmaceutically acceptable carrier.

[0011] The present invention also relates to methods for supplementingnutritional deficiencies in a patient or person by administering acomposition comprising carotenoids, vitamin E, vitamin D, vitamin C,thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin,pantothenic acid, cobalamin, magnesium, manganese, zinc, selenium,chromium, copper, alpha lipoic acid, and lutein, wherein thiscomposition is free of added iron.

[0012] The methods of the present invention may be used to treatpatients suffering from anorexia, malnutrition, gastrointestinaldisorders, chronic alcoholism, chronic infections, acute infections,congestive heart failure, hyperthyroidism, poorly controlled diabetes,cheilosis, gingivitis, stomatitis, and dietary restrictions. Inaddition, these methods may be used to treat the nutritionaldeficiencies in patients suffering from a disease state that results inincreased oxidative stress or elevated homocysteine levels.

[0013] In a preferred embodiment, the methods of the present inventionutilize compositions comprising carotenoids in a range of about 2400 IUto about 3600 IU, vitamin E in a range of about 80 IU to about 120 IU,vitamin D in a range of about 320 IU to about 480 IU, vitamin C in arange of about 240 mg to 360 mg, thiamine in a range of about 16 mg toabout 24 mg, riboflavin in a range of about 4 mg to about 6 mg, niacinin a range of about 20 mg to about 30 mg, folic acid in a range of about0.8 mg to about 1 mg, pyridoxine provided in a range of about 20 mg toabout 30 mg, biotin in a range of about 80 μg to about 120 μg,pantothenic acid in a range of about 12 mg to about 18 mg, cobalamin ina range of about 40 μg to about 60 μg, magnesium in a range of about 40mg to about 60 mg, manganese in a range of about 1.2 mg to about 1.8 mg,zinc in a range of about 20 mg to about 30 mg, selenium in a range ofabout 80 μg to about 120 μg, chromium in a range of about 40 μg to about60 μg, copper in a range of about 1.2 mg to about 1.8 mg copper, lipoicacid in a range of about 12 mg to about 18 mg, and lutein in a rangefrom about 4 mg to about 6 mg, wherein these compositions are free ofadded iron.

[0014] In a further preferred embodiment, the methods of the presentinvention utilize a composition comprising about 3000 IU carotenoids,about 100 IU d-alpha tocopheryl succinate, about 400 IU vitamin D₃,about 300 mg vitamin C, about 20 mg thiamine, about 5 mg riboflavin,about 25 mg niacinamide, about 1.0 mg folic acid, about 25 mg pyridoxineHCl, about 100 μg biotin, about 15 mg calcium pantothenate, about 50 μgcyanocobalamin, about 50 mg magnesium oxide, about 1.5 mg manganesesulfate, about 25 mg zinc oxide, about 100 μg selenium, about 50 μgchromium chloride, about 1.5 mg cupric sulfate, about 15 mg alpha lipoicacid, and about 5 mg lutein, wherein this composition is free of addediron.

DETAILED DESCRIPTION

[0015] Proper nutrition is essential for maintaining health andpreventing diseases. The compositions and methods of the presentinvention provide the means to optimize good health by utilizingvitamin, mineral, and antioxidant nutritional supplementation. Morespecifically, the compositions of the present invention contain avariety of antioxidants, which may minimize free radical concentrationsand minimize the deleterious effects of oxidative stress, and vitaminsand minerals that support normal levels of homocysteine. It is to beunderstood that the terminology used herein is used for the purpose ofdescribing particular embodiments only, and is not intended to limit thescope of the present invention. It must be noted that as used herein andin the appended claims, the singular forms “a,” “an,” and “the” includeplural reference unless the context clearly dictates otherwise.

[0016] The compositions of the present invention may preferably compriseantioxidant factors that may protect against oxidative stress. Oxidativestress occurs as the body's natural use of oxygen creates unstablemolecules known as free radicals, which steal stable electron partnersfrom other molecules, launching more free radicals and increasedmolecular and cellular instability. This ‘oxidative stress’ isimplicated in over 200 diseases, including cardiovascular disease andcancer, which are attributed to free radical oxidation. Rock et al., 96J. AM. DIETARY ASSOC. 693-702 (1996). For example, lipid peroxidation isthe initiating step in the oxidation of low-density lipoproteins (LDL).In turn, the lipid peroxides oxidate other lipoproteins, which are takenup by the cells of the arterial wall. Eventually, the deposited oxidizedlipoproteins form an atherosclerotic plaque. Id. The antioxidantcomponents of the compositions and methods described herein maypreferably include one or more of vitamin E, selenium, vitamin C,carotenoids, lutein, and lipoic acid.

[0017] The compositions and methods of the present invention also maypreferably include B-complex vitamins, which are critical for health aseach is part of one or more coenzymes in metabolizing food properly.This class of vitamins is water-soluble nutrients, not storedsignificantly in the body. Importantly, the B-complex vitamins may helpnormalize homocysteine levels and metabolism. High homocysteine levelshave been correlated directly with increased risk of atherosclerosis andother heart disease. Although the exact mechanism by which homocysteinecontributes to heart disease is not fully understood, it may act as anendothelial irritant that promotes atherosclerosis by inducingendothelial dysfunction. B-complex vitamins are required for the properfunction of the homocysteine metabolic pathway, thus maintainingadequate levels of these vitamins may assist in normalizing homocysteinelevels and maintaining good health. The B-complex vitamins of thepresent compositions and methods may preferably include one or more ofthiamin (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid, biotin,folic acid, pyridoxine (B₆) and cobalamin (B₁₂).

[0018] Minerals are inorganic, or non-carbon-containing, elements thatare critical for healthy physiological processes, and are contemplatedin the compositions and methods of the present invention. For example,minerals act as cofactors for hundreds of enzymes that range from thoseassociated, for example, with food digestion, nucleic acid production,protein synthesis to antioxidant enzymes. One particular mineral,chromium, is essential in healthy insulin function, as it plays a directrole in insulin's interactions at the cellular level. The minerals ofthe compositions and methods of the present invention may preferablyinclude one or more of chromium, zinc, copper, magnesium, and manganese.

[0019] Another mineral, iron, is specifically excluded from thecompositions and methods of the present invention. Although iron is anessential mineral with many functions, iron has also been implicated asa catalyst for lipid oxidation. Specifically, lipid oxidation associatedwith LDL cholesterol has been correlated strongly with an increased riskof cardiovascular disease. Moreover, some older patients exhibitsensitivity to iron or build-up of iron concentration in the liver.Although iron supplementation may be indicated in specific populationgroups or disease states, universal supplementation may not always berecommended. Hence, the compositions and methods of the presentinvention are preferably free of added iron.

[0020] Vitamin D may preferably be a component of the compositions andmethods of the present invention. Vitamin D is a fat-soluble “hormonelike” substance essential for healthy bones. This vitamin increases theabsorption of calcium and phosphorous from the gastrointestinal tract,and improves essential mineral resorption into bone tissue. Vitamin Dcan be converted to its active form from exposure of the skin tosunlight. This fact is among the reasons why vitamin D deficiency iscommon in the elderly, notably the institutionalized, who spend littleor no time out of doors. Deficiencies lead to increased bone turnoverand loss, and when severe, osteomalacia or softening of the bones.Supplementation with vitamin D has been shown to moderately reduce boneloss, increase serum 25-hydroxyvitamin D, and decrease serum parathyroidhormone levels. Dawson-Hughes et al., 337 NEW ENG. J. MED. 670-76(1997); Lips et al., 86 J. CLIN. ENDOCRINOL. METAB. 1212-21 (2001).

[0021] Preferably, the vitamin D of the compositions and methods of thepresent invention is vitamin D₃. In the body, vitamin D₃ is producedwhen its precursor is exposed to ultraviolet irradiation (e.g.,sunlight) and then hydroxylated in the liver to form 25-hydroxyvitaminD₃, the major form of vitamin D in the circulation. This form of thevitamin may be hydroxylated again in the kidney, yielding 1,25hydroxyvitamin D₃, the most potent form of vitamin D. As noted above,vitamin D₃ plays a role in the maintenance of calcium and phosphorushomeostasis, but it is also active in cell differentiation and immunefunction. In a preferred embodiment of the invention, vitamin D₃ ispresent in the amount ranging from about 320 IU to about 480 IU. In aparticularly preferred embodiment, vitamin D₃ is present in an amount ofabout 400 IU.

[0022] As discussed previously, the antioxidant components of thecompositions and methods described herein preferably include vitamin E,selenium, vitamin C, carotenoids, lutein, and lipoic acid.

[0023] Vitamin E is a fat-soluble vitamin antioxidant found inbiological membranes where it protects the phospholipid membrane fromoxidative stress. More specifically, alpha-tocopherol, the most abundantand most active form of the vitamin E family, is the principlelipid-soluble, chain breaking antioxidant in tissue and plasma.RECOMMENDED DIETARY ALLOWANCES 99-101 (Nat'l Research Council, 10th ed.,1989) (hereinafter “RDA”). Vitamin E inhibits the oxidation ofunsaturated fatty acids by trapping peroxyl free radicals. It is also anantiatherogenic agent, and studies have demonstrated a reduced risk ofcoronary heart disease with increased intake of vitamin E. Stampfer etal., 328 New Eng. J. MED. 1444-49 (1993). Vitamin E is available invarious forms known to those of skill in the art. In a preferredembodiment of the present invention, vitamin E is present in an amountranging from about 80 IU to about 120 IU. In a particularly preferredembodiment of the invention, vitamin E is present d-alpha tocopherylsuccinate. A preferred embodiment of the invention includes about 100 IUd-alpha tocopheryl succinate.

[0024] Along with vitamin E, the mineral selenium is a component of theantioxidant enzyme, glutathione peroxidase, which plays a critical rolein the control of oxygen metabolism, particularly catalyzing thebreakdown of hydrogen peroxide. Burk, 3 ANN. REV. NUTRITION 53-70(1983). Glutathione peroxidase prevents the generation of free radicalsand decreases the risk of oxidative damage to numerous tissues,including the vascular system. Holben, 99 J. AM. DIETARY Assoc. 836-43(1999). Another selenoprotein is the enzyme iodothyronine 5′-diodinasethat converts thyroxine (T₄) to triiodothyronine (T₃). Selenium isavailable in many forms known to those of ordinary skill in the art. Ina preferred embodiment of the present invention, selenium is included ina range of about 80 μg to about 120 μg. In a preferred embodiment of theinvention, selenium is present as sodium selenate. A preferredembodiment of the invention includes about 100 μg sodium selenate.

[0025] Vitamin C (also known as ascorbic acid) is another antioxidantpresent in the invention described herein. The major biochemical role ofthe water-soluble vitamin C is as a co-substrate in metal catalyzedhydroxylations, and it has antioxidant properties in interactingdirectly with superoxide hydroxyl radicals and singlet oxygen. Vitamin Calso provides antioxidant protection for folate and vitamin E, keepingvitamin E in its most potent form. It also enhances the absorption ofiron. RDA, at 115. In addition, vitamin C is required for collagensynthesis, epinephrine synthesis, and bile acid formation. Moreover,vitamin C has been implicated in inhibiting atherosclerosis by beingpresent in extracellular fluid of the arterial wall and potentiatingnitric oxide activity, thus normalizing vascular function. A preferredembodiment of the compositions of the present invention includes asupplemental dose of vitamin C, preferably in the amount of about 240 mgto about 360 mg. A preferred embodiment of the present inventionincludes about 300 mg of vitamin C.

[0026] Along with vitamins E and C, and selenium, carotenoids are agroup of antioxidants embodied in the present invention. There are over600 carotenoids occurring naturally in fruits and vegetables. Many ofthese fat-soluble compounds, of which beta-carotene is a well-knownexample, have pro-vitamin A activity as well as antioxidant activity.Less-known carotenoids include alpha-carotene, lutein, cryptoxanthine,and zeaxanthin. The compositions and methods herein include a cartonoidcomplex that closely mirrors that found naturally in fruits andvegetables. In particular, the carotenoids of the present invention maypreferably include alpha-carotene, beta-carotene, cryptoxanthin, lutein,and zeaxanthin. In particular, lutein and zeaxanthin are the majorcarotenoids that make up the macular pigment of the eye's retina, andtheir antioxidant properties protect the eye from light-induced damageand macular degeneration. Berendschot et al., 41 INVEST. OPHTHALMOL.VIS. SCI. 3322-26 (2000). In a preferred embodiment of the invention,carotenoids are included in a range of about 2400 IU to about 3600 IU.In a more preferred embodiment of the invention, the carotenoids includea mixture of alpha-carotene, beta-carotene, cryptoxanthin, lutein, andzeaxanthin. A preferred embodiment of the invention includes about 3000IU of a mixture of alpha-carotene, beta-carotene, cryptoxanthin, lutein,and zeaxanthin.

[0027] Lutein is also preferably included in the compositions andmethods described herein and is preferably included in an amountdistinguished from that included in the mixed carotenoids. Regarding theantioxidant activity of lutein, scientists have demonstrated that luteinis an effective antioxidant capable of scavenging peroxyl radicals andquenching reactive oxygen species. Rapp et al., 41 INVEST. OPHTHALMOL.VIS. SCI. 1200-09 (2000). Thus, the compositions and methods of thepresent invention may include lutein, preferably in the amount rangingfrom about 4 mg to about 6 mg. A preferred embodiment of the inventioncomprise about 5 mg lutein.

[0028] Lipoic acid is an antioxidant and is preferably included in thecompositions and methods of the present invention. Known as the“universal antioxidant,” alpha lipoic acid is both a lipid- andwater-soluble antioxidant that works synergistically with otherantioxidants in the cell's mitochondria. In addition to working withother antioxidant nutrients, lipoic acid has powerful, pro-antioxidantenzyme properties. Alpha lipoic acid is also a cofactor for severalregulatory enzymes, including pyruvate dehydrogenase, and appears tohave an effect on glucose transport and utilization. Rudich et al., 42DIABETOLOGIA 949-57 (1999). Alpha lipoic acid also increases tocopherolactivity and acts as a metal chelator. Furthermore, alpha lipoic acidimproves microvascular perfusion. Haak et al., 108 EXPERIMENTAL &CLINICAL ENDOCRINOLOGY & DIABETES 168-74 (2000). A preferred embodimentof the compositions of the present invention comprises alpha lipoic acidin the amount ranging from about 12 mg to about 18 mg. A particularlypreferred embodiment of the present invention comprises about 15 mg oflipoic acid.

[0029] In addition to antioxidants, the compositions and methods of thepresent invention also preferably include one or more B-complex vitaminssuch as thiamin (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid(B₅), biotin, folic acid, pyridoxine (B₆) and cobalamin (B₁₂).

[0030] Thiamine (vitamin B₁) plays a role in carbohydrate metabolism andneural function. It is a coenzyme for the oxidative decarboxylation ofalpha-ketoacids (e.g., alpha-ketoglutarate and pyruvate) and fortransketolase which is a component of the pentose phosphate pathway.Folate deficiency and malnutrition inhibit the activity of thiamine.RDA, at 123. One embodiment of the compositions of the present inventionmay comprise thiamine, preferably in the amount ranging from about 16 mgto about 24 mg. In a preferred embodiment of the present invention, theform of thiamine is thiamine HCl. A preferred embodiment of theinvention comprises about 20 mg thiamine HCl.

[0031] Riboflavin (vitamin B₂) is a component of two flavin coenzymes,flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Theseflavoenzymes are involved in a number of oxidation-reduction reactionsincluding the conversion of pyridoxine and niacin. RDA, at 132.Flavoenzymes also play a role in a number of metabolic pathways such ascitric acid cycle, amino acid deamination, purine degradation, and fattyacid oxidation and thus help to maintain carbohydrate, amino acid, andlipid metabolism. In one embodiment, the compositions and methods of thepresent invention comprise riboflavin, preferably in the amount rangingfrom about 4 mg to about 6 mg. A preferred embodiment of the inventioncomprises about 5 mg of riboflavin.

[0032] Niacin, also called vitamin B₃, is the common name for twocompounds: nicotinic acid (also called niacin) and niacinamide (alsocalled nicotinamide). Niacin and is particularly important formaintaining healthy levels and types of fatty acids. Niacin is alsorequired for the synthesis of pyroxidine, riboflavin, and folic acid.RDA, at 137. Administration of niacin may also produce a reduction intotal cholesterol, LDL, and very low density lipoprotein (VLDL) levels;and an increase in high density lipoprotein (HDL) cholesterol levels.Nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) areactive coenzymes of niacin. These coenzymes are involved in numerousenzymatic reactions such as glycolysis, fatty acid metabolism, andsteroid synthesis. Henkin et al., 91 AM. J. MED. 239-46 (1991). Oneembodiment of the compositions and methods of the present invention maycomprise niacin, preferably in the amount ranging from about 20 mg toabout 30 mg. In a preferred embodiment of the invention, niacin ispresent in the form of niacinamide. A preferred embodiment of theinvention comprises about 25 mg of niacinamide.

[0033] Folic acid (vitamin B₈), also called folate or methylfolate, isessential for the formation of red and white blood cells within bonemarrow and also plays a role in heme formation. RDA, at 150. Folic acidin its active form, tetrahydrofolate, is a coenzyme that is involved inthe transfer of methyl groups and it plays a role in DNA synthesis,purine synthesis, and amino acid synthesis, such as the conversion ofglycine to serine and the transformation of homocysteine to methionine.The activation of folic acid requires a vitamin B₁₂-dependenttransmethylation and vitamin B₁₂ is also necessary for folic aciddelivery to tissues. Id. One embodiment of the compositions and methodsof the present invention may comprise folic acid, preferably in theamount ranging from about 0.8 mg to about 1.0 mg. A preferred embodimentof the invention comprises about 1 mg of folic acid.

[0034] Pyridoxine (vitamin B₆) is another B-complex vitamin included inthe compositions and methods described herein. The administration ofpyridoxine may reduce the levels of homocysteine. Bostom et al., 49KIDNEY INT. 147-52 (1996). The active forms of pyridoxine,pyridoxal-5′-phosphate (PLP) and pyridoxamine-5′-phosphate, arecoenzymes for numerous enzymes and as such, are essential forgluconeogenesis, niacin formation, and erythrocyte metabolism. RDA, at142-143. Pyridoxine is a coenzyme for both cystathionine synthase andcystathionase, enzymes that catalyze the formation of cysteine frommethionine. Homocysteine is an intermediate in this process and elevatedlevels of plasma homocysteine are recognized as a risk factor forvascular disease. Robinson et al., 94 CIRCULATION 2743-48 (1996). Hence,one embodiment of the compositions and methods of the present inventionmay comprise pyridoxine, preferably in the amount ranging from about 20mg to about 30 mg. In a preferred embodiment of the invention,pyridoxine is in the form of pyridoxine HCl. A preferred embodiment ofthe invention comprises about 25 mg pyridoxine HCl.

[0035] Biotin, another water-soluble B-complex vitamin, acts a coenzymefor a number of carboxylases, and thus has an important role ingluconeogenesis, fatty acid metabolism, and amino acid metabolism. RDA,at 166. For example, biotin serves as a carboxyl carrier for pyruvatecarboxylase, which is involved in gluconeogenesis; acetyl CoAcarboxylase, which is involved in fatty acid synthesis; andpropionyl-CoA carboxylase, which is involved in glucose production.Researchers believe that biotin inhibits the effects of uremic toxins ontubulin polymerizaton. Braguer et al., 57 NEPHRON 192-96 (1991). Thus,one embodiment of the compositions and methods of the present inventioncomprises biotin, preferably in the amount ranging from about 80 μg toabout 120 μg. A preferred embodiment of the invention comprises about100 μg biotin.

[0036] Pantothenic acid (vitamin B₅) is a component of both the coenzymeA macromolecule and the acyl-carrier protein. These coenzymes functionas carriers for acyl groups and are required for the synthesis of fattyacids, cholesterol, steroid hormones, and neurotransmitters. Thecoenzyme A complex also has a major role in the acetylation andacylation of numerous proteins. RDA, at 169. One embodiment of thecompositions and methods of the present invention comprises pantothenicacid, preferably in the amount ranging from about 12 mg to about 18 mg.In a preferred embodiment of the invention, pantothenic acid is presentas calcium pantothenate. A preferred embodiment of the inventioncomprises about 15 mg calcium pantothenate.

[0037] Cobalamin (vitamin B₁₂), another important vitamin included inthe compositions and methods described herein, can be converted to theactive coenzymes, methylcobalamin and 5′-deoxyadenosylcobalamin. Thesecoenzymes are necessary for folic acid metabolism, conversion ofcoenzyme A, and myelin synthesis. For example, methylcobalamin catalyzesthe demethylation of a folate cofactor, which is involved in DNAsynthesis. A lack of demethylation may result in folic acid deficiency.RDA, at 159-160. Deoxyadenosylcobalamin is the coenzyme for theconversion of methylmalonyl-CoA to succinyl-CoA, which plays a role inthe citric acid cycle. Importantly, cobalamin, along with pyridoxine andfolic acid in implicated in the proper metabolism of homocysteine.Cobalamin is available as cyanocobalamin, methylcobalamin,hydroxocobalamin, adenosylcobalamin, and hydroxycyanocobalamin. Oneembodiment of the compositions and methods of the present invention maycomprise cobalamin, preferably in the amount ranging from about 40 μg toabout 60 μg. In a preferred embodiment of the invention, cobalamin ispresent as cyanocobalamin. A preferred embodiment of the inventionincludes about 50 μg cyanocobalamin.

[0038] As noted previously, minerals are inorganic elements that play acrucial role in physiological processes in the body relating to goodhealth. The compositions and methods of the present invention maycomprise minerals, and, in a preferred embodiment, comprise one or moreof selenium, discussed above, and magnesium, manganese, zinc, chromium,and copper.

[0039] Magnesium is found primarily in both bone and muscle. Magnesiumis an essential component for over 300 enzymes, including enzymes ofbiosynthetic pathways, glycolysis, protein synthesis, transketolasereactions, and membrane transport. Magnesium is also involved in theformation of cAMP, a cytosolic second messenger that plays a role incell signaling mechanisms. In addition, magnesium functions bothsynergistically and antagonistically with calcium in neuromusculartransmission. RDA, at 188. Specifically, magnesium is critical for themaintenance of electrochemical potentials of nerve and muscle membranesand the neuromuscular junction transmissions, particularly important inthe heart. Not surprisingly, magnesium deficiency is tied tocardiovascular disease and hypertension. Agus et al., 17 CRIT. CARECLINICS 175-87 (2001). Indeed, oral magnesium therapy improvesendothelial function in patients with coronary disease. Shechter et al.,102 CIRCULATION 2353-58 (2000). Yet, most individuals in the U.S.receive only about seventy-five percent of the magnesium they need fromtheir diets. Magnesium is available in a variety of salts. Oneembodiment of the compositions and methods of the present inventioncomprises magnesium, preferably in the amount ranging from about 40 mgto about 60 mg. In a preferred embodiment of the invention, magnesium ispresent as magnesium oxide. A preferred embodiment of the inventioncomprises about 50 mg magnesium oxide.

[0040] Manganese, like magnesium, plays a key role in multiple enzymesand is needed for healthy skin, bone, and cartilage formation, as wellas glucose tolerance. For example, manganese is a cofactor for enzymessuch as glutamine synthetase, pyruvate carboxylase, and mitochrondrialsuperoxide dismutase. RDA, at 230. In particular, manganese is essentialfor glycoprotein and proteoglycan synthesis, and thus is involved in theformation of connective and skeletal tissue, as well as carbohydrate andlipid metabolism. It also helps activate superoxide dismutase, animportant antioxidant enzyme. Manganese is available in many forms knownto those of ordinary skill in the art, including manganese sulfate,manganese oxide, manganese oxy-sulfate, and manganese proteinate. Oneembodiment of the compositions and methods of the present inventioncomprises manganese, preferably in the amount ranging from about 1.2 mgto about 1.8 mg. In a preferred embodiment, manganese is present asmanganese sulfate. A preferred embodiment of the invention comprisesabout 1.5 mg of manganese sulfate.

[0041] Zinc plays a role in numerous metabolic activities such asnucleic acid production, protein synthesis, and development of theimmune system. There are more than 200 zinc metalloenzymes includingaldolase, alcohol dehydrogenase, RNA polymerase, and protein kinase C.Zima et al., 17 BLOOD PURIF. 182-86 (1999). Moreover, zinc stabilizesRNA and DNA structures, forms zinc fingers in nuclear receptors, and isa component of chromatin proteins involved in transcription andreplication. Zinc is available in many forms, such as zinc oxide andzinc sulfate. One embodiment of the compositions and methods of thepresent invention comprises zinc, preferably in the amount ranging fromabout 20 mg to about 30 mg. More preferably, zinc may be present as zincoxide. A preferred embodiment of the invention comprises about 25 mgzinc oxide.

[0042] The trace mineral chromium harmonizes with insulin at thecellular level to optimize the release of energy from glucose, as wellas maintaining proper cellular lipid or fat metabolism. Specifically,chromium increases insulin binding to cells, insulin receptor number,and activates the insulin receptor kinase leading to increased insulinsensitivity. Several studies suggest that adequate chromium levels areneeded for optimal glycemic control. See, e.g., Anderson et al., 26DIABETES METABOLABOLISM 22-27 (2000); Vincent, 130 J. NUTRITION 715-18(2000). The concentration of chromium declines with age, and coronaryartery disease appears to be associated with low levels of chromium.RDA, at 241. Yet, ninety percent of adults in the U.S. consume less thanthe recommended minimum amount of chromium. Chromium is available invarious forms known to those skilled in the art, such as chromiumchloride, chromium sulfate, chromium potassium sulfate, and chromiumpicolinate. One embodiment of the compositions and methods of thepresent invention comprises chromium, preferably in the amount rangingfrom about 40 μg to about 60 μg. Preferably, chromium is supplied aschromium chloride. A preferred embodiment of the invention comprises 50μg chromium chloride.

[0043] Copper is a component of several enzymes associated with numerousphysiological functions, including, for example, oxidase enzymes, suchas cytochrome c oxidase, and cytosolic superoxide dismutase. RDA, at224. In particular, copper is a cofactor of lysyl oxidase, which iscritical for lysine cross-linking in collagen and elastin. Copper actsas an antioxidant, and promotes the synthesis of melanin andcatecholamines. In addition, copper is present in the blood asceruloplasmin which is involved in oxidizing iron prior to transport tothe plasma. Copper is available in multiple forms, such as cupric oxide,copper sulfate, cupric acetate, and alkaline copper carbonate. Oneembodiment of the compositions and methods of the present inventioncomprises copper, preferably in the amount ranging from about 1.2 mg toabout 1.8 mg. In a preferred embodiment of the invention, coppercomprises cupric sulfate. A preferred embodiment comprises about 1.5 mgcupric sulfate.

[0044] The compositions and methods of the present invention represent acombination of essential vitamins and minerals that work together withvarious metabolic systems and physiological responses of the human body.The active ingredients are available from numerous commercial sources,and in several active forms or salts thereof, known to those of ordinaryskill in the art. Hence, the compositions and methods of the presentinvention are not limited to any particular form of the vitamin ormineral ingredient described herein.

[0045] The ingredients of the present invention are preferably combinedinto a composition which may be in the form of a solid powder, caplets,tablets, lozenges, pills, capsules, or a liquid, and which may beadministered alone or in suitable combination with other components. Forexample, the composition of the present invention may be administered inone or more caplets or lozenges as practical for ease of administration.Each of the vitamins and minerals is commercially available, and can beblended to form a single composition or can form multiple compositions,which may be co-administered.

[0046] To prepare the compositions of the present invention, each of theactive ingredients may be combined in intimate admixture with a suitablecarrier according to conventional compounding techniques. The carriermay take a wide variety of forms depending upon the form of thepreparation desired for administration, e.g., oral, sublingual, nasal,topical patch, or parenteral. Preferably, the composition may consistsof one to three caplets or lozenges, the composition of each beingidentical to each other caplet or lozenge.

[0047] In preparing the composition in oral dosage form, any of theusual media may be utilized. For liquid preparations (e.g., suspensions,elixirs, and solutions), media containing, for example water, oils,alcohols, flavoring agents, preservatives, coloring agents and the likemay be used. Carriers such as starches, sugars, diluents, granulatingagents, lubricants, binders, disintegrating agents and the like may beused to prepare oral solids (e.g., powders, caplets, pills, tablets,capsules, and lozenges). Controlled release forms may also be used.Because of their ease in administration, caplets, tablets, pills, andcapsules represent the most advantageous oral dosage unit form, in whichcase solid carriers are employed. If desired, tablets may be sugarcoated or enteric coated by standard techniques. All of thesepharmaceutical carriers and formulations are well known to those ofordinary skill in the art. See, e.g., WADE & WALLER, HANDBOOK OFPHARMACEUTICAL EXCIPIENTS (2nd ed. 1994).

[0048] Other objectives, features and advantages of the presentinvention will become apparent from the following specific examples. Thespecific examples, while indicating specific embodiments of theinvention, are provided by way of illustration only. Accordingly, thepresent invention also includes those various changes and modificationswithin the spirit and scope of the invention that may become apparent tothose skilled in the art from this detailed description. The inventionwill be further illustrated by the following non-limiting examples.

EXAMPLE 1

[0049] A composition of the following formulation was prepared in capletform, including the appropriate excipients, by standard methods known tothose of ordinary skill in the art: Carotenoids 3000 IU (Alpha-Carotene,Beta-Carotene, Cryptoxanthin, Lutein, Zeaxanthin) Vitamin E 100 IUVitamin D₃ 400 IU Vitamin C (Ascorbic Acid) 300 mg Vitamin B₁ (ThiamineHCl) 20 mg Vitamin B₂ (Riboflavin) 5 mg Niacin (Niacinamide) 25 mg FolicAcid 1 mg Vitamin B₆ (Pyridoxine HCl) 25 mg Biotin 100 μg PantothenicAcid (Calcium Pantothenate) 15 mg Vitamin B₁₂ (Cyanocobalamin) 50 μgMagnesium (Magnesium Oxide) 50 mg Manganese (Manganese Sulfate) 1.5 mgZinc (Zinc Oxide) 25 mg Selenium (Sodium Selenate) 100 μg Chromium(Chromium Chloride) 50 μg Copper (Cupric Sulfate) 1.5 mg Alpha LipoicAcid 15 mg Lutein 5 mg

EXAMPLE 2

[0050] A study is undertaken to evaluate the effectiveness of thecomposition of the present invention in the treatment of patients. Theobjective of the study is to determine whether oral intake of thecomposition results in an improvement of the nutritional status of thepatient, either therapeutically or prophylacticly.

[0051] A double-blind, placebo controlled study is conducted over atwelve-month period. A total of sixty subjects (30 men and 30 women),aged 40 to 85 years, suffering from dietary restrictions or a diseasestate such as anorexia, malnutrition, gastrointestinal disorders,chronic alcoholism, chronic infections, acute infections, congestiveheart failure, hyperthyroidism, poorly controlled diabetes, cheilosis,gingivitis, sensitivity to iron, hemosiderosis, hemochromatosis, orstomatitis, or a propensity or disposition to such a disease state arechosen for the study. An initial assessment of nutritional status isconducted utilizing methods such as the peroxide hemolysis test toassess vitamin E deficiency, measurement of erythrocyte transketolaseactivity to determine thiamine levels, determination of erythrocyteglutathione reductase activity to assess riboflavin status, and highperformance liquid chromatography to directly measure PLP and pyridoxinelevels.

[0052] The sixty subjects are separated into two separate groups offifteen men and fifteen women. In the first group, each subject isadministered 1 to 2 caplets, daily, of the composition as described inExample 1. In the second group (control), each subject is administered 1to 2 placebo caplets, daily.

[0053] An assessment of nutritional status for each subject is measuredat one-month intervals for a twelve month period as described above andthe data is evaluated using multiple linear regression analysis and astandard students t-test. In each analysis the baseline value of theoutcome variable is included in the model as a covariant. Treatment bycovariant interaction effects is tested by the method outlined by Weigel& Narvaez, 12 CONTROLLED CLINICAL TRIALS 378-94 (1991). If there are nosignificant interaction effects, the interaction terms are removed fromthe model. The regression model assumptions of normality and homogeneityof variance of residuals are evaluated by inspection of the plots ofresiduals versus predicted values. Detection of the temporal onset ofeffects is done sequentially by testing for the presence of significanttreatment effects at 16, 12, and 8 weeks, proceeding to the earlier timein sequence only when significant effects have been identified at eachlater time period. Changes from the baseline within each group areevaluated using paired t-tests. In addition, analysis of variance isperformed on all baseline measurements and measurable subjectcharacteristics to assess homogeneity between groups. All statisticalprocedures are conducted using the Statistical Analysis System (SASInstitute Inc., Cary, N.C.). An alpha level of 0.05 is used in allstatistical tests.

[0054] A statistically significant improvement in the nutritional statusis preferably observed in the treated subjects upon completion of thestudy over the controls. The study may also look at the progression ofthe disease state, or the prevention or delay of a disease or diseasestate, or the reduction of the severity of a disease. The differencesbetween nutritional state or the progression of the disease state, orthe prevention or delay of a disease or disease state, or the reductionof the severity of a disease, between the treated subjects and controlsare preferably statistically significant and or observable by clinicalor other tests or evaluations. Therefore, the study confirms that oraladministration of the composition of the present invention is effectiveas a nutritional supplement, either therapeutically or prophylacticly,for example, in preventing the severity or delaying or preventing theonset of a disease.

[0055] While there has been described what is presently believed to bethe preferred embodiments of the present invention, other and furthermodifications and changes may be made without departing from the spiritof the invention. All further and other modifications and changes areincluded that come within the scope of the invention as set forth in theclaims. The disclosure of all publications cited above are expresslyincorporated by reference in their entireties to the same extent as ifeach were incorporated by reference individually.

We claim:
 1. A composition for supplementing nutritional deficiencies ina patient or person in need thereof, comprising carotenoids, vitamin E,vitamin D, vitamin C, thiamine, riboflavin, niacin, folic acid,pyridoxine, biotin, pantothenic acid, cobalamin, magnesium, manganese,zinc, selenium, chromium, copper, alpha lipoic acid, and lutein; whereinsaid composition is free of added iron.
 2. The composition of claim 1,wherein said carotenoids are present in the range of about 2400 IU toabout 3600 IU.
 3. The composition of claim 1, wherein said carotenoidscomprise at least one carotenoid selected from the group consisting ofalpha-carotene, beta-carotene, cryptoxanthin, lutein, and zeaxanthin. 4.The composition of claim 3, wherein said carotenoid is present in theamount of about 3000 IU.
 5. The composition of claim 1, wherein saidvitamin E is present in the range of about 80 IU to about 120 IU.
 6. Thecomposition of claim 1, wherein said vitamin E comprises d-alphatocopheryl succinate.
 7. The composition of claim 6, wherein saidvitamin E is present in the amount of about 100 IU.
 8. The compositionof claim 1, wherein said vitamin D is in the range of about 320 IU toabout 480 IU.
 9. The composition of claim 1, wherein said vitamin Dcomprises vitamin D₃.
 10. The composition of claim 9, wherein saidvitamin D is present in the amount of about 400 IU.
 11. The compositionof claim 1, wherein said vitamin C is in the range of about 240 mg toabout 360 mg.
 12. The composition of claim 1, wherein said vitamin C isin the amount of about 300 mg.
 13. The composition of claim 1, whereinsaid thiamine is in the range of about 16 mg to about 24 mg.
 14. Thecomposition of claim 1, wherein said thiamine comprises thiamine HCl.15. The composition of claim 14, wherein said thiamine is present in theamount of about 20 mg.
 16. The composition of claim 1, wherein saidriboflavin is present in the range of about 4 mg to about 6 mg.
 17. Thecomposition of claim 1, wherein said riboflavin is present in the amountof about 5 mg.
 18. The composition of claim 1, wherein said niacin ispresent in the range of about 20 mg to about 30 mg.
 19. The compositionof claim 1, wherein said niacin comprises niacinamide.
 20. Thecomposition of claim 19, wherein said niacin is present in the amount ofabout 25 mg.
 21. The composition of claim 1, wherein folic acid ispresent in the range of about 0.8 mg to about 1.0 mg.
 22. Thecomposition of claim 1, wherein said folic acid is present in the amountof about 1 mg.
 23. The composition of claim 1, wherein said pyridoxineis present in the range of about 20 mg to about 30 mg.
 24. Thecomposition of claim 1, wherein said pyridoxine comprises pyridoxineHCl.
 25. The composition of claim 24, wherein said pyridoxine is presentin the amount of about 25 mg.
 26. The composition of claim 1, whereinsaid biotin is present in the range of about 80 μg to about 120 μg. 27.The composition of claim 1, wherein said biotin is present in the amountof about 100 μg.
 28. The composition of claim 1, wherein saidpantothenic acid is present in the range of about 12 mg to about 18 mg.29. The composition of claim 1, wherein said pantothenic acid comprisescalcium pantothenate.
 30. The composition of claim 29, wherein saidpantothenic acid is present in the amount of about 15 mg.
 31. Thecomposition of claim 1, wherein said cobalamin is present in the rangeof about 40 μg to about 60 μg.
 32. The composition of claim 1, whereinsaid cobalamin comprises cyanocobalamin.
 33. The composition of claim32, wherein said cobalamin is present in the amount of about 50 μg. 34.The composition of claim 1, wherein said magnesium is present in therange of about 40 mg to about 60 mg.
 35. The composition of claim 1,wherein said magnesium comprises magnesium oxide.
 36. The composition ofclaim 35, wherein said magnesium is present in the amount of about 50mg.
 37. The composition of claim 1, wherein said manganese is present inthe range of about 1.2 mg to about 1.8 mg.
 38. The composition of claim1, wherein said manganese comprises manganese sulfate.
 39. Thecomposition of claim 38, wherein said manganese is present in the amountof about 1.5 mg.
 40. The composition of claim 1, wherein said zinc ispresent in the range of about 20 mg to about 30 mg.
 41. The compositionof claim 1, wherein said zinc comprises zinc oxide.
 42. The compositionof claim 41, wherein said zinc is present in the amount of about 25 mg.43. The composition of claim 1, wherein said selenium is present in therange of about 80 μg to about 120 μg.
 44. The composition of claim 1,wherein said selenium comprises sodium selenate.
 45. The composition ofclaim 44, wherein said selenium is present in the amount of about 100μg.
 46. The composition of claim 1, wherein said chromium is present inthe range of about 40 μg to about 60 μg.
 47. The composition of claim 1,wherein said chromium comprises chromium chloride.
 48. The compositionof claim 47, wherein said chromium is present in the amount of about 50μg.
 49. The composition of claim 1, wherein said copper is present inthe range of about 1.2 mg to about 1.8 mg.
 50. The composition of claim1, wherein said copper comprises cupric sulfate.
 51. The composition ofclaim 50, wherein said copper is present in the amount of about 1.5 mg.52. The composition of claim 1, wherein said alpha lipoic acid ispresent in the range of about 12 mg to about 18 mg.
 53. The compositionof claim 1, wherein said alpha lipoic acid is present in the amount ofabout 15 mg.
 54. The composition of claim 1, wherein said lutein is inthe range of about 4 mg to about 6 mg.
 55. The composition of claim 1,wherein said lutein is present in the amount of about 5 mg.
 56. Acomposition for supplementing nutritional deficiencies in a patient orperson in need thereof, comprising about 2400 IU to about 3600 IUcarotenoids, about 80 IU to about 120 IU vitamin E, about 320 IU toabout 480 IU vitamin D, about 240 mg to about 360 mg vitamin C, about 16mg to about 24 mg thiamine, about 4 mg to about 6 mg riboflavin, about20 mg to about 30 mg niacin, about 0.8 mg to about 1.2 mg folic acid,about 20 mg to about 30 mg pyridoxine, about 80 μg to about 120 μgbiotin, about 12 mg to about 18 mg pantothenic acid, about 40 μg toabout 60 μg cobalamin, about 40 mg to about 60 mg magnesium, about 1.2mg to about 1.8 mg manganese, about 20 mg to about 30 mg zinc, about 80μg to about 120 μg selenium, about 40 μg to about 60 μg chromium, about1.2 mg to about 1.8 mg copper, about 12 mg to about 18 mg alpha lipoicacid, and about 4 mg to about 6 mg lutein; wherein said composition isfree of added iron.
 57. The composition of claim 56, wherein saidcomposition comprises about 3000 IU carotenoids, about 100 IU vitamin E,about 400 IU vitamin D, about 300 mg vitamin C, about 20 mg thiamine,about 5 mg riboflavin, about 25 mg niacin, about 1.0 mg folic acid,about 25 mg pyridoxine, about 100 μg biotin, about 15 mg pantothenicacid, about 50 μg cyanocobalamin, about 50 mg magnesium, about 1.5 mgmanganese, about 25 mg zinc, about 100 μg selenium, about 50 μgchromium, about 1.5 mg copper, about 15 mg alpha lipoic acid, and about5 mg lutein.
 58. The composition of claim 56, wherein said compositionis administered to said patient daily.
 59. The composition of claim 56,wherein said composition is administered to said patient orally.
 60. Thecomposition of claim 56, wherein said composition further comprises apharmaceutically acceptable carrier.
 61. A method for supplementingnutritional deficiencies in a patient or person in need thereof,comprising administering to a patient or a person a compositioncomprising carotenoids, vitamin E, vitamin D, vitamin C, thiamine,riboflavin, niacin, folic acid, pyridoxine, biotin, pantothenic acid,cobalamin, magnesium, manganese, zinc, selenium, chromium, copper, alphalipoic acid, and lutein; wherein said composition is free of added iron.62. The method of claim 61, wherein said carotenoids are present in therange of about 2400 IU to about 3600 IU.
 63. The method of claim 61,wherein said carotenoids comprise at least one carotenoid selected fromthe group consisting of alpha-carotene, beta-carotene, cryptoxanthin,lutein, and zeaxanthin.
 64. The method of claim 63, wherein saidcarotenoid is present in the amount of about 3000 IU.
 65. The method ofclaim 61, wherein said vitamin E is present in the range of about 80 IUto about 120 IU.
 66. The method of claim 61, wherein said vitamin Ecomprises d-alpha tocopheryl succinate.
 67. The method of claim 66,wherein said vitamin E is present in the amount of about 100 IU.
 68. Themethod of claim 61, wherein said vitamin D is present in the range ofabout 320 IU to about 480 IU.
 69. The method of claim 61, wherein saidvitamin D comprises D₃.
 70. The method of claim 69, wherein said vitaminD is present in the amount of about 400 IU.
 71. The method of claim 61,wherein said vitamin C is present in the range of about 240 mg to about360 mg.
 72. The method of claim 61, wherein said vitamin C is present inthe amount of about 300 mg.
 73. The method of claim 61, wherein saidthiamine is present in the range of about 16 mg to about 24 mg.
 74. Themethod of claim 61, wherein said thiamine comprises thiamine HCl. 75.The method of claim 74, wherein said thiamine is present in the amountof about 20 mg.
 76. The method of claim 61, wherein said riboflavin ispresent in the range of about 4 mg to about 6 mg.
 77. The method ofclaim 61, wherein said riboflavin is in the amount of about 5 mg. 78.The method of claim 61, wherein said niacin is present in the range ofabout 20 mg to about 30 mg.
 79. The method of claim 61, wherein saidniacin comprises niacinamide.
 80. The method of claim 79, wherein saidniacin is present in the amount of about 25 mg.
 81. The method of claim61, wherein folic acid is present in the range of about 0.8 mg to about1.0 mg.
 82. The method of claim 61, wherein said folic acid is presentin the amount of about 1 mg.
 83. The method of claim 61, wherein saidpyridoxine is present in the range of about 20 mg to about 30 mg. 84.The method of claim 61, wherein said pyridoxine comprises pyridoxineHCl.
 85. The method of claim 84, wherein said pyridoxine is present inthe amount of about 25 mg.
 86. The method of claim 61, wherein saidbiotin is present in the range of about 80 g to about 120 μg.
 87. Themethod of claim 61, wherein said biotin is present in the amount ofabout 100 μg.
 88. The method of claim 61, wherein said pantothenic acidis present in the range of about 12 mg to about 18 mg.
 89. The method ofclaim 61, wherein said pantothenic acid comprises calcium pantothenate.90. The method of claim 89, wherein said pantothenic acid is present inthe amount of about 15 mg.
 91. The method of claim 61, wherein saidcobalamin is present in the range of about 40 μg to about 60 μg.
 92. Themethod of claim 61, wherein said cobalamin comprises cyanocobalamin. 93.The method of claim 92, wherein said cobalamin is present in the amountof about 50 μg.
 94. The method of claim 61, wherein said magnesium ispresent in the range of about 40 mg to about 60 mg.
 95. The method ofclaim 61, wherein said magnesium comprises magnesium oxide.
 96. Themethod of claim 95, wherein said magnesium is present in the amount ofabout 50 mg.
 97. The method of claim 61, wherein said manganese ispresent in the range of about 1.2 mg to about 1.8 mg.
 98. The method ofclaim 61, wherein said manganese comprises manganese sulfate.
 99. Themethod of claim 98, wherein said manganese is present in the amount ofabout 1.5 mg.
 100. The method of claim 61, wherein said zinc is presentin the range of about 20 mg to about 30 mg.
 101. The method of claim 61,wherein said zinc comprises zinc oxide.
 102. The method of claim 101,wherein said zinc is present in the amount of about 25 mg.
 103. Themethod of claim 61, wherein said selenium is present in the range ofabout 80 μg to about 120 μg.
 104. The method of claim 61, wherein saidselenium comprises sodium selenate.
 105. The method of claim 104,wherein said selenium is present in the amount of about 100 μg.
 106. Themethod of claim 61, wherein said chromium is present in the range ofabout 40 μg to about 60 μg.
 107. The method of claim 61, wherein saidchromium comprises chromium chloride.
 108. The method of claim 107,wherein said chromium is present in the amount of about 50 μg.
 109. Themethod of claim 61, wherein said copper is present in the range of about1.2 mg to about 1.8 mg.
 110. The method of claim 61, wherein said coppercomprises cupric sulfate.
 111. The method of claim 110, wherein saidcopper is present in the amount of about 1.5 mg.
 112. The method ofclaim 61, wherein said alpha lipoic acid is present in the range ofabout 12 mg to about 18 mg.
 113. The method of claim 61, wherein saidalpha lipoic acid is present in the amount of about 15 mg.
 114. Themethod of claim 61, wherein said lutein is present in the range of about4 mg to about 6 mg.
 115. The method of claim 61, wherein said lutein ispresent in the amount of about 5 mg.
 116. A method for supplementingnutritional deficiencies in a patient or person in need thereof,comprising administering to a patient or a person a compositioncomprising about 2400 IU to about 3600 IU carotenoids, about 80 IU toabout 120 IU vitamin E, about 320 IU to about 480 IU vitamin D, about240 mg to about 360 mg vitamin C, about 16 mg to about 24 mg thiamine,about 4 mg to about 6 mg riboflavin, about 20 mg to about 30 mg niacin,about 0.8 mg to about 1.2 mg folic acid, about 20 mg to about 30 mgpyridoxine, about 80 μg to about 120 μg biotin, about 12 mg to about 18mg pantothenic acid, about 40 μg to about 60 μg cobalamin, about 40 mgto about 60 mg magnesium, about 1.2 mg to about 1.8 mg manganese, about20 mg to about 30 mg zinc, about 80 μg to about 120 μg selenium, about40 μg to about 60 μg chromium, about 1.2 mg to about 1.8 mg copper,about 12 mg to about 18 mg alpha lipoic acid, and about 4 mg to about 6mg lutein; wherein said composition is free of added iron.
 117. Themethod of claim 116, wherein said composition comprises about 3000 IUcarotenoids, about 100 IU vitamin E, about 400 IU vitamin D, about 300mg vitamin C, about 20 mg thiamine, about 5 mg riboflavin, about 25 mgniacin, about 1.0 mg folic acid, about 25 mg pyridoxine, about 100 μgbiotin, about 15 mg pantothenic acid, about 50 μg cyanocobalamin, about50 mg magnesium, about 1.5 mg manganese, about 25 mg zinc, about 100 μgselenium, about 50 μg chromium, about 1.5 mg copper, about 15 mg alphalipoic acid, and about 5 mg lutein.
 118. The method of claim 116,wherein said composition is administered to said patient daily.
 119. Themethod of claim 116, wherein said composition is administered to saidpatient orally.
 120. The method of claim 116, wherein said compositionfurther comprises a pharmaceutically acceptable carrier.
 121. Thecomposition of claim 1, wherein said nutritional deficiencies are aresult of dietary restrictions.
 122. The composition of claim 1, whereinsaid nutritional deficiencies are a result of a disease state.
 123. Thecomposition of claim 122, wherein said disease state is selected fromone or more of the group consisting of anorexia, malnutrition,gastrointestinal disorders, chronic alcoholism, chronic infections,acute infections, congestive heart failure, hyperthyroidism, poorlycontrolled diabetes, cheilosis, gingivitis, hemochromatosis,hemosiderosis, and stomatitis.
 124. The composition of claim 122,wherein said disease state leads to increased oxidative stress in saidpatient.
 125. The composition of claim 122, wherein said disease stateleads to elevated homocysteine levels in said patient.
 126. Thecomposition of claim 56, wherein said nutritional deficiencies are aresult of dietary restrictions.
 127. The composition of claim 56,wherein said nutritional deficiencies are a result of a disease state.128. The composition of claim 127, wherein said disease state isselected from one or more of the group consisting of anorexia,malnutrition, gastrointestinal disorders, chronic alcoholism, chronicinfections, acute infections, congestive heart failure, hyperthyroidism,poorly controlled diabetes, cheilosis, gingivitis, hemochromatosis,hemosiderosis and stomatitis.
 129. The composition of claim 127, whereinsaid disease state leads to increased oxidative stress in said patient.130. The composition of claim 127, wherein said disease state leads toelevated homocysteine levels in said patient.
 131. The method of claim61, wherein said nutritional deficiencies are a result of dietaryrestrictions.
 132. The method of claim 61, wherein said nutritionaldeficiencies are a result of a disease state.
 133. The method of claim132, wherein said disease state is selected from one or more of thegroup consisting of anorexia, malnutrition, gastrointestinal disorders,chronic alcoholism, chronic infections, acute infections, congestiveheart failure, hyperthyroidism, poorly controlled diabetes, cheilosis,gingivitis, hemochromatosis, hemosiderosis and stomatitis.
 134. Themethod of claim 132, wherein said disease state leads to increasedoxidative stress in said patient.
 135. The method of claim 132, whereinsaid disease state leads to elevated homocysteine levels in saidpatient.
 136. The method of claim 116, wherein said nutritionaldeficiencies are a result of dietary restrictions.
 137. The method ofclaim 116, wherein said nutritional deficiencies are a result of adisease state.
 138. The method of claim 137, wherein said disease stateis selected from one or more of the group consisting of anorexia,malnutrition, gastrointestinal disorders, chronic alcoholism, chronicinfections, acute infections, congestive heart failure, hyperthyroidism,poorly controlled diabetes, cheilosis, gingivitis, hemochromatosis,hemosiderosis and stomatitis.
 139. The method of claim 137, wherein saiddisease state leads to increased oxidative stress in said patient. 140.The method of claim 137, wherein said disease state leads to elevatedhomocysteine levels in said patient.